ALTERATIONS IN ELASTIN AND COLLAGEN RELATED TO THE MECHANISM OF PROGRESSIVE PULMONARY VENOUS OBSTRUCTION IN A PIGLET MODEL - A HEMODYNAMIC, ULTRASTRUCTURAL, AND BIOCHEMICAL-STUDY
ALTERATIONS IN ELASTIN AND COLLAGEN RELATED TO THE MECHANISM OF PROGRESSIVE PULMONARY VENOUS OBSTRUCTION IN A PIGLET MODEL - A HEMODYNAMIC, ULTRASTRUCTURAL, AND BIOCHEMICAL-STUDY
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DOI：
10.1161/01.res.66.2.438
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发表时间：
1990-02-01
影响因子：
20.1
通讯作者：
RABINOVITCH, M
中科院分区：
文献类型：
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作者：
LABOURENE, JI;COLES, JG;RABINOVITCH, M
我们创建了一个动物模型，以更好地了解进行性中央肺静脉（PV）阻塞的发病机制和潜在机制，这种情况不适用于当前的治疗。 20 头仔猪接受了 PV 环扎，18 头仔猪进行了假手术，并进行了相关的未手术对照。 1、3和6周后，获得血流动力学数据，并将其与心室重量、PV和肺动脉（PA）扩张性（1周时）、形态结构和超微结构分析以及通过重量分析（以及1周时通过锁链素水平）测定的弹性蛋白的生化评估、胶原蛋白和弹性蛋白酶活性相关联。第 1 周时，PV 条带与 PV 依从性增加相关 (p < 0.05)。第 3 周时，观察到 PA 压力 (Ppa) 增加（p < 0.05），但 PV 压力 (Pcw) 没有增加。然而，在 PV 中，内弹性层破裂，平滑肌细胞明显从中层迁移至内皮下层。 6 周时，观察到 Pcw 上升（p < 0.01）、Ppa 进一步上升（p < 0.01）和右心室肥厚（p < 0.005）。我们还观察到PV内膜轻度增厚（p < 0.01）、弹性层完全降解（p < 0.05）以及形态学评估的胶原蛋白增加（p < 0.01）。绑扎过程导致 PV 弹性蛋白合成和通过重量分析确定的弹性蛋白比例总体增加（两者均 p < 0.05），但不是通过锁链素水平确定，这表明弹性蛋白先前交联的可能性，这可能是 PV 早期扩张性增加的原因。然而，我们的测定无法检测到与弹性蛋白降解的扩张性增加或超微结构变化相关的弹性蛋白酶活性的增加。 Ppa 的增加与显着的 PA 生化或结构变化无关。我们推测，为了应对远端静脉阻塞，PV 的早期重塑会增加扩张性，保护肺部免受静脉充血的影响并抑制 Pcw 的上升。 PA 高血压先于 Pcw 升高，可能是由于反射性血管收缩所致。随后 Pcw 的小幅上升已经与 PV 的广泛纤维化相关，这表明当前治疗不成功的原因以及需要考虑早期评估和干预。
We created an animal model to understand better the pathogenesis and underlying mechanism of progressive central pulmonary venus (PV) obstruction, a condition not amenable to current therapy. Twenty piglets underwent banding of their PVs, 18 had a sham operation, and correlated nonoperated controls. After 1, 3, and 6 weeks hemodynamic data were obtained and correlated with ventricular weights, PV and pulmonary artery (PA) distensibilities (at 1 week), morphometric structural and ultrastructural analyses, and biochemical assessment of elastin determined gravimetrically (and by desmosine level at 1 week), collagen, and elastase activity. At 1 week, PV banding was associated with increased PV compliance (p < 0.05). At 3 weeks, an increased PA pressure (Ppa) (p < 0.05) was observed, unaccompanied by a rise in PV pressure (Pcw). In the PV, however, there was breakdown of the internal elastic lamina with apparent migration of smooth muscle cells from media to subendothelium. At 6 weeks, a rise in Pcw (p < 0.01), a further rise in Ppa (p < 0.01), and right ventricular hypertrophy (p < 0.005) were observed. We also observed mild PV intimal thickening (p < 0.01), complete degradation of elastic laminae (p < 0.05), and an increase in collagen assessed morphometrically (p < 0.01). The banding procedure resulted in an overall increase in PV elastin synthesis and in the proportion of elastin determined gravimetrically (p < 0.05 for both) but not by desmosine level, suggesting the possibility of prior cross-linking of elastin, which might account for the early increased distensibility of the PV. However, our assay could not detect an increase in elastase activity associated with either the increased distensibility or the ultrastructural changes of elastin degradation. The increased Ppa was not associated significant PA biochemical or structural changes. We speculate that in response to distal venous obstruction, early remodeling of the PVs increases distensibility, protecting the lung from venous congestion and blunting a rise in Pcw. PA hypertension precedes the rise in Pcw, likely because of reflex vasoconstriction. The subsequent modest rise in Pcw is already associated with extensive fibrosis of the PV, suggesting a reason for unsuccessful current therapy and a need for consideration of earlier assessment and intervention.